Plain English Summary
Background and study aims
A stroke occurs when the blood supply to part of the brain is cut off, either due to a blood clot (an ischaemic stroke) or a blood vessel bursting (a haemorrhagic stroke). Stroke can lead to cognitive decline and dementia. Intensive lowering of blood pressure and/or lipids (LDL-cholesterol) may reduce the risk of dementia after stroke. The aim of this study is to find out whether intensive blood pressure and/or lipid lowering are better than moderate blood pressure and/or lipid lowering to prevent cognitive decline after stroke.
Who can participate?
Patients who have had an ischaemic or haemorrhagic stroke in the last three to seven months.
What does the study involve?
Participants with ischaemic stroke are randomly allocated to either moderate or intensive blood pressure lowering treatment and to either moderate or intensive lipid lowering treatment. Participants with haemorrhagic stroke are randomly allocated to either moderate or intensive blood pressure lowering treatment. The study is testing treatment strategies, not individual drugs.
What are the possible benefits and risks of participating?
Not provided at time of registration
Where is the study run from?
Nottingham University Hospitals NHS Trust (UK)
When is the study starting and how long is it expected to run for?
January 2010 to January 2018
Who is funding the study?
1. The Stroke Association (UK)
2. The Alzheimer's Society (UK)
Who is the main contact?
Prof. Philip Bath
Philip.Bath@nottingham.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Prof Philip Bath
ORCID ID
Contact details
Division of Stroke Medicine
Institute of Neuroscience
Clinical Sciences Building
City Hospital Campus
Hucknall Road
Nottingham
NG5 1PB
United Kingdom
+44 (0)115 8231765
Philip.Bath@nottingham.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
Version 1.0
Study information
Scientific title
Prevention Of Decline in Cognition After Stroke Trial (PODCAST): a factorial randomised controlled trial of intensive versus guideline (moderate) lowering of blood pressure and lipids
Acronym
PODCAST
Study hypothesis
To study if intensive blood pressure and/or lipid lowering post stroke, is better than moderate blood pressure and/or lipid lowering, to prevent cognitive decline after stroke.
Ethics approval
Nottingham Research Ethics Committee 1, 24/07/2009
Study design
Multicentre prospective randomised open-label blinded end-point controlled partial-factorial phase IV trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Cognitive impairment after stroke
Intervention
The trial will assess whether intensive blood pressure lowering (systolic blood pressure less than 125 mmHg) and lipid lowering (low density lipoprotein [LDL]-cholesterol less than 2.0 mmol/L) is better than moderate blood pressure lowering (systolic blood pressure less than 140 mmHg) and cholesterol lowering (LDL-cholesterol less than 3.0 mmol/L).
Participants with ischaemic stroke will be randomised to both the blood pressure and lipid lowering arms; participants with haemorrhagic stroke will be randomised only to the blood pressure lowering arm.
The study will test management strategies and not individual drugs. Algorithms taking account of 'National Institute of Clinical Excellence, UK Guidelines', relating to stroke, hypertension, lipids and Type 2 Diabetes will aid investigators in treatment decision-making using standard antihypertensive and lipid lowering drugs so that participants are treated as randomised.
The total duration of the trial is 8 years and follow up for participants will range from 1 - 8 years depending on the time of enrolment. The trial intervention will be for the same duration.
Intervention type
Other
Phase
Phase IV
Drug names
Primary outcome measure
Comparison of cognition (Addenbrooke's Cognitive Examination extended to include death) between 'intensive' and 'moderate' BP/lipid lowering groups, measured at baseline, 6, 18, 30, 42, 54, 66, 78, 90 and 96 months.
Secondary outcome measures
For each of BP-lowering and lipid-lowering arms, comparison between 'intensive' and 'moderate' groups:
1. Dementia: measured at 6, 18, 30, 42, 54, 66, 78, 90 and 96 months -
1.1. Using alzheimers disease (AD) - National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and vascular dementia (VaD) - National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherché et l'Enseignement en Neurosciences (NINDS-AIREN)
1.2. With/without recurrent stroke
2. Cognition: all tests at 6, 18, 30, 42, 54, 66, 78, 90 and 96 months, except telephone-administered mini-mental state examination (tMMSE) and Telephone Interview for Cognitive Status (TICS-M) done at 0, 12, 24, 36, 48, 70 and 84 months over the telephone
2.1. Global - mini-mental state examination (MMSE), tMMSE, TICS
2.2. Association - trail making A/B
2.3. STROOP test
2.4. Cognitive decline with/without recurrent stroke
2.5. Ordinal cognition (MMSE greater than 28/23 - 28/10 - 22/less than 10/dementia/dead)
2.6. Informant (IQCODE)
3. Quality of life - EuroQoL, informant (DEMQoL), measured at baseline, 6, 18, 30, 42, 54, 66, 78, 90 and 96 months
4. Depression (Zung), measured at baseline, 6, 18, 30, 42, 54, 66, 78, 90 and 96 months
5. Dependency (modified Rankin Scale [mRS]), measured at baseline, 6, 18, 30, 42, 54, 66, 78, 90 and 96 months
6. Disability (Barthel Index [BI]), measured at baseline, 6, 18, 30, 42, 54, 66, 78, 90 and 96 months
7. Stroke recurrence, measured at baseline and every six months until the end of the trial
8. Myocardial infarction, measured every six months until the end of the trial
9. Composite vascular events (non-fatal stroke, non-fatal MI, fatal vascular), measured every six months until the end of the trial
10. Stroke: fatal/severe non-fatal/mild/transient ischaemic attack [TIA]/none, measured at baseline and every six months until the end of the trial
11. Myocardial infarction: fatal/non-fatal/angina/none, measured at baseline and every six months until the end of the trial
12. Vascular: fatal/non-fatal/none, measured at baseline and every six months until the end of the trial
13. New diabetes, measured at baseline, 6, 18, 30, 42, 54, 66, 78, 90 and 96 months
14. New atrial fibrillation, measured at baseline, 6, 18, 30, 42, 54, 66, 78, 90 and 96 months
15. Residence (home, institution), care package, informal family support, measured at baseline, 6, 18, 30, 42, 54, 66, 78, 90 and 96 months
16. Blood pressure (systolic BP, diastolic BP, pulse pressure, rate-pressure product), measured at baseline, 6, 18, 30, 42, 54, 66, 78, 90 and 96 months
17. Lipids (total cholesterol [TC], triglycerides [TG], HDL, calculated LDL), measured at baseline, 6, 18, 30, 42, 54, 66, 78, 90 and 96 months
18. Neuroimaging (in a subset of participants), measured at baseline and at 3 years
Overall trial start date
01/01/2010
Overall trial end date
01/01/2018
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Age greater than 70 years and telephone-administered mini-mental state examination (MMSE) greater than 16; or aged greater than 60 years and telephone-MMSE 17 - 19, either sex
2. Functionally independent (modified Rankin Scale [mRS] 0 - 2)
3. Ischaemic stroke (any cortical Oxfordshire Community Stroke Project [OCSP]/Trial of ORG 10172 in Acute Stroke Treatment [TOAST] type) or primary intracerebral haemorrhage (cortical or basal ganglia)
4. Three to seven months post-event (to allow cognitive, neurological, blood pressure [BP] and lipid stabilisation, but avoid attrition)
5. Systolic BP 125 - 170 mmHg
6. Total cholesterol 3 - 8 mmol/l
7. Presence of a reporter: partner, sibling, child, friend (for Informant Questionnaire of Cognitive Decline [IQCODE]/Dementia Quality of Life [DEMQoL])
8. Capacity and willingness to give consent
Participant type
Patient
Age group
Senior
Gender
Both
Target number of participants
3400 participants (600 in the start-up phase and 2800 in the main phase)
Participant exclusion criteria
1. Participants not meeting inclusion criteria
2. Subarachnoid haemorrhage
3. Secondary intracranial haemorrhage (trauma, arteriovenous malformation [AVM], cavernoma)
4. Posterior circulation ischaemic stroke
5. Posterior circulation haemorrhage
6. No computed tomography (CT)/magnetic resonance imaging (MRI) during index stroke
7. Inability to give consent or do study measures, e.g. severe dysphasia, weakness of dominant arm
8. Severe hypertension (systolic BP greater than 170 mmHg)
9. Definite need for 'intensive' BP control
10. Severe hypercholesterolemia (total cholesterol [TC] greater than 8 mmol/l)
11. Definite need for 'high intensity' statin or ezetimibe
12. Definite need for a cholinesterase inhibitor
13. Familial stroke associated with dementia, e.g. cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL)
14. Chronic renal failure: glomerular filtration rate (GFR) less than 50
15. Liver disease, alanine aminotransferase (ALT) greater than 60
16. Ongoing participation in trials involving drug and/or devices, or within the last 3 months
Recruitment start date
01/01/2010
Recruitment end date
01/01/2018
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Institute of Neuroscience
Notttingham
NG5 1PB
United Kingdom
Sponsor information
Organisation
The University of Nottingham (UK)
Sponsor details
c/o Mr Paul Cartledge
Head of Research Grants and Contracts
Research Innovation Services
King's Meadow Campus
Lenton Lane
Nottingham
NG7 2NR
United Kingdom
+44 (0)115 951 5679
paul.cartledge@nottingham.ac.uk
Sponsor type
University/education
Website
Funders
Funder type
Charity
Funder name
Stroke Association (UK) (ref: TSA2008/09)
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
Associations and societies (private and public)
Location
United Kingdom
Funder name
Alzheimer's Society (UK) (ref: TSA 2008/09)
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
Associations and societies (private and public)
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2013 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/24266960
2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/26545986
2017 results in: http://www.ncbi.nlm.nih.gov/pubmed/28095412
Publication citations
-
Protocol
Blackburn DJ, Krishnan K, Fox L, Ballard C, Burns A, Ford GA, Mant J, Passmore P, Pocock S, Reckless J, Sprigg N, Stewart R, Wardlaw J, Bath PM, Prevention of Decline in Cognition after Stroke Trial (PODCAST): a study protocol for a factorial randomised controlled trial of intensive versus guideline lowering of blood pressure and lipids., Trials, 2013, 14, 401, doi: 10.1186/1745-6215-14-401.